At the end of the day, only you can decide when you've had enough of the game. ;)
Agency missions, faction missions and the stronghold takeovers are the only structured "missions" within the game. However there are several actions that count towards completion as measured within the game. These actions are:
- Completing challenges (i.e. races, shown by the checkered flag icons on the map)
- Discovering locations (undiscovered locations shown by yellow dots on the map)
- Destroying Sabotage Destructible Objects
- Collecting resource items (Vehicle Parts, Armor Parts, Weapon Parts, Cash Stashes)
- Collecting faction items (Skulls, Black Boxes, Drug Drops - shown by blue dots on the map)
- Destroying Baby Panay Statues
- Assassinating Colonels
- Destroying pipeline stations (by hacking them)
All locations than can be discovered can be "completed" by performing the above actions within that settlement. All settlements will contain resource items, most will contain destructible objects, and some will contain a Panay Statue, Colonel or a pipeline (I think no more than one of these per location - certainly more than this is very rare). Completed settlements show on the map as the settlement icon with a green tick through the middle of it.
Completing challenges and collecting faction items does not count towards settlement completion - only towards total game completion.
Note that a few glitches mean it may not be possible to reach 100% game completion. The highest completion level required by a game achievement is 75% for the Perfectionist achievement.
In addition there are a slew of other achievements/trophies that are not tied to the above criteria, such as for killing enemies in creative ways, driving all the different vehicles, flying under bridges and so on.